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NSAID steroid update

Leo Semes, OD, FAAO

I. Mechanisms of action – the role of a. Mediators of inflammation b. … and much more

II. Topical NSAIDS – ophthalmic application

III. Oral NSAIDs a. Precautions and contraindications b. Pain moderation and amelioration c. OTC/Rx // Alternative recommendations d. NSAIDs vs. narcotic

Learning Objectives

1. To understand mechanisms of inflammation and pain 2. To appreciate strategies topical and oral for management of inflammation and pain 3. To appreciate alternatives to Rx medications for oral pain and inflammation management The Oxford League Table (modified from: http://www.medicine.ox.ac.uk/bandolier/booth/painpag/acutrev/analgesics/lftab.html; accessed and modified 6/6/10)

( = acetaminophen)

The 2007 Oxford league table of efficacy

Numbers needed to treat (NNT)are calculated for the proportion of patients with at least 50% pain relief over 4-6 hours compared with placebo in randomized, double-blind, single- dose studies in patients with moderate to severe pain. Drugs were oral, unless specified, and doses are mg. Shaded rows are intramuscular administration

Analgesic Number of Percent NNT Lower Higher patients in with at confidence confidence comparison least 50% interval interval pain relief

* 180/240 248 77 1.5 1.3 1.7

*Etoricoxib 100/120 500 70 1.6 1.5 1.8

* 40 (Bextra©) 473 73 1.6 1.4 1.8

**Dipyrone 1000 113 79 1.6 1.3 2.2

Ibuprofen 600/800 165 86 1.7 1.4 2.3

Valdecoxib 20 204 68 1.7 1.4 2.0

(Bextra©)

Ketorolac 20 69 57 1.8 1.4 2.5

Toradol©; (Acular, Acular LS, Acuvai, topical)

Ketorolac 60 116 56 1.8 1.5 2.3 (intramuscular)

Diclofenac 100 545 69 1.8 1.6 2.1

Piroxicam 40 30 80 1.9 1.2 4.3

(Feldene©)

Celecoxib 400 298 52 2.1 1.8 2.5 Celebrex©

Paracetamol 1000 + 197 57 2.2 1.7 2.9 60

Oxycodone IR 5 + 150 60 2.2 1.7 3.2 Paracetamol 500

Bromfenac 25 370 51 2.2 1.9 2.6

Rofecoxib 50 675 54 2.3 2.0 2.6

Vioxx©

Oxycodone IR 15 60 73 2.3 1.5 4.9

Aspirin 1200 279 61 2.4 1.9 3.2

Bromfenac 50 247 53 2.4 2.0 3.3

Dipyrone 500 288 73 2.4 1.9 3.2

Ibuprofen 400 5456 55 2.5 2.4 2.7

Bromfenac 100 95 62 2.6 1.8 4.9

Oxycodone IR 10 + 315 66 2.6 2.0 3.5 Paracetamol 650

Diclofenac 25 502 53 2.6 2.2 3.3

Ketorolac 10 790 50 2.6 2.3 3.1

Paracetamol 650 + 679 43 2.6 2.3 3.0 75

Oxycodone IR 83 67 2.7 1.7 5.6 10+Paracetamol 1000

Naproxen 400/440 197 51 2.7 2.1 4.0

Piroxicam 20 280 63 2.7 2.1 3.8

* 400 370 48 2.7 2.2 3.5

Prexige© 500/550 784 52 2.7 2.3 3.3

Diclofenac 50 1296 57 2.7 2.4 3.1

Ibuprofen 200 3248 48 2.7 2.5 2.9

Dextropropoxyphene 130 50 40 2.8 1.8 6.5

(Davron©)

Paracetamol 650 + 201 60 2.8 2.1 4.4 tramadol 112

Bromfenac 10 223 39 2.9 2.3 4.0

Pethidine 100 364 54 2.9 2.3 3.9 (intramuscular)

Tramadol 150 561 48 2.9 2.4 3.6

(Ultram©, Tramol©)

Morphine 10 946 50 2.9 2.6 3.6 (intramuscular)

Naproxen 200/220 202 45 3.4 2.4 5.8

Ketorolac 30 359 53 3.4 2.5 4.9 (intramuscular)

Paracetamol 500 561 61 3.5 2.2 13.3

Celecoxib 200 805 40 3.5 2.9 4.4

Paracetamol 1500 138 65 3.7 2.3 9.5

Ibuprofen 100 495 36 3.7 2.9 4.9

Oxycodone IR 5 + 78 55 3.8 2.1 20.0 Paracetamol 1000

Paracetamol 1000 2759 46 3.8 3.4 4.4

Paracetamol 600/650 + 1123 42 4.2 3.4 5.3 Codeine 60 Paracetamol 650 + 963 38 4.4 3.5 5.6 (65 mg hydrochloride or 100 mg napsylate)

Aspirin 600/650 5061 38 4.4 4.0 4.9

Paracetamol 600/650 1886 38 4.6 3.9 5.5

Ibuprofen 50 316 32 4.7 3.3 8.0

Tramadol 100 882 30 4.8 3.8 6.1

Tramadol 75 563 32 5.3 3.9 8.2

Aspirin 650 + Codeine 60 598 25 5.3 4.1 7.4

Oxycodone IR 5 + 149 24 5.5 3.4 14.0 Paracetamol 325

Ketorolac 10 142 48 5.7 3.0 53.0 (intramuscular)

Paracetamol 300 + 379 26 5.7 4.0 9.8 Codeine 30

Bromfenac 5 138 20 7.1 3.9 28.0

Tramadol 50 770 19 8.3 6.0 13.0

Codeine 60 1305 15 16.7 11.0 48.0

Placebo >10,000 18 N/A N/A N/A

*not FDA-approved

** for veterinary use only

IV. (http://www.fda.gov/Drugs/DrugSafety/PostmarketDrugSafetyInformationforPatientsand Providers/ucm150314.htm; accessed 6/6/10)

COX-2 Selective Non-steroidal Anti-inflammatory Drugs (NSAIDs) and Prescription and Over-the- Counter (OTC) Non-selective NSAIDs Approved Under New Drug Application (NDA) Abbreviated New Drug Application (ANDA)

COX-2 Selective NSAIDs Chemical Name Brand Name Celecoxib Celebrex Valdecoxib Bextra Vioxx

Non-selective NSAIDs Chemical Name Brand Name Cataflam, Voltaren, Arthrotec (combination with Diclofenac ) Dolobid Lodine, Lodine XL Nalfon, Nalfon 200 Ansaid Ibuprofen** Motrin, Motrin IB, Motrin Migraine Pain, Advil, Advil Migraine Liqui-gels, Ibu-Tab 200, Medipren, Cap-Profen, Tab-Profen, Profen, Ibuprohm, Children’s Elixsure *, Vicoprofen (combination with ), Combunox (combination with oxycodone) Indomethacin Indocin, Indocin SR, Indo-Lemmon, Indomethagan ** Oruvail, Orudis, Actron Ketorolac Toradol Ponstel Mobic Relafen Naproxen** Aleve, Naprosyn, Anaprox, Anaprox DS, EC- Naproxyn, Naprelan, Naprapac (copackaged with lansoprazole) Daypro Piroxicam Feldene Disalcid Clinoril Tolectin, Tolectin DS, Tolectin 600

*There are many OTC Combinations with ibuprofen: Advil Cold And Sinus, Advil Cold, Advil Allergy Sinus, Children’s Advil Allergy Sinus, Ibuprohm Cold and Sinus, Sine-Aid IB, Children’s Motrin Cold.

**There are over-the-counter versions of these prescription medications.